The purpose of this research program is to analyze the effects of halogenated amphetamines, particularly fenfluramine (FFA), on the mammalian central nervous system. Research in progress indicates that FFA has a significant toxicity on serotonin neurons of the midbrain raphe. Administration of FFA results in histological changes demonstrable 3 to 7 days after a single 100 micrometer/kg dose. These changes are found with conventional aldehyde fixation but are not evident in material fixed with Bouin's solution. In studies to be conducted during the next year, the nature of these changes will be characterized further with light and electron microscopy. An analysis of the effects of chronic, low dose FFA on brainstem serotonin neurons will be carried out. Further experiments will investigate the effects of FFA on axoplasmic transport of protein in serotonin neurons innervating forebrain. Lastly, ultrastructural studies will be directed toward analysis of acute effects of FFA on terminals of serotonin neurons.